A diet high in fructose can increase uric acid levels, but allopurinol may help lower the resulting high blood pressure, researchers say.

Action Points

Explain that patients who took allopurinol to mitigate the effects of a high-fructose diet had a decrease in uric acid and had no increase in blood pressure, unlike patients on the same diet who didn't take the drug.

A diet high in fructose can increase uric acid levels, but allopurinol may help lower the resulting high blood pressure, researchers say.

Men who took the drug to mitigate the effects of a high-fructose diet did not experience the increase in blood pressure observed among men on the same diet who did not take the drug, Richard Johnson, MD, of the University of Colorado, and colleagues said at the American Heart Association's High Blood Pressure Research Conference in Chicago.

"These results support the idea that fructose, such as present in table sugar and high-fructose corn syrup, could have a role in the epidemic of obesity and metabolic syndrome," Johnson said. "Further, they suggest that [the two sweeteners] could have a role in high blood pressure, and that this might be mediated by uric acid."

Eating a lot of fructose -- typically from sugary drinks sweetened with high-fructose corn syrup -- has previously been associated with increased levels of uric acid.

"It has been known for a long time that fructose can raise uric acid levels, and in the last few years epidemiological studies have also confirmed that those with the highest fructose intake have higher uric acid levels," Johnson said.

"Reducing sugar intake was an old treatment for gout as well, and was even espoused by Sir William Osler," the renowned physician widely credited with advancing modern medicine.

Robert Lustig, MD, of the University of California San Francisco, was a co-author on a paper in the Journal of Pediatrics published last summer that found evidence of this link in adolescents. The more sugary beverages the teens consumed, the greater their serum uric acid levels and, hence, their systolic blood pressure.

"The fact that this paper addresses this mechanism in humans rather than just rats is extremely important," Lustig said.

But he cautioned that uric acid is likely not the only cause of the metabolic syndrome.

"I absolutely think that uric acid is the main driver of hypertension" with regard to fructose consumption, Lustig said. "But it may not be the driver of the visceral adiposity, the dyslipidemia," and other components of the metabolic syndrome.

Still, Johnson and colleagues wanted to know whether allopurinol, which is primarily used to treat gout, could combat the blood-pressure-increasing effects of a high-fructose diet.

So they evaluated 74 adult men who were put on a diet that included 200 grams of fructose a day, on top of their regular diet (typically, people in the U.S. consume about 50 to 70 grams of fructose per day).

Half of the men were randomized to allopurinol.

After two weeks, those who weren't on the drug had a 6 mm Hg-increase in systolic blood pressure and a 3 mm Hg-increase in diastolic pressure (P<0.004 and P<0.007, respectively).

On the other hand, those on allopurinol had no increase in diastolic pressure and a nonsignificant 1 mm Hg-increase in systolic pressure, Johnson said.

In addition, markers of the metabolic syndrome increased among men eating lots of fructose but not taking allopurinol. Incidence of the disease jumped from 19% at baseline to 44% after two weeks, Johnson said.

For this group, mean fasting triglycerides increased by about 55 mg/dL while HDL cholesterol fell by about 2.5 mg/dL (P<0.002 and P<0.001, respectively).

For those on allopurinol, Johnson said there was a lowering of LDL cholesterol compared with controls. But there was no reduction in HOMA scores or triglyceride levels.

"I think there's more to it than just uric acid," Lustig said. "Uric acid is responsible for hypertension, but dyslipidemia is due to other effects in the liver on lipid pathways. There are other ways fructose induces these problems."

Fructose is one of the sweetest naturally occurring sugars and is frequently found in fruits, some vegetables, honey, and some other plants. What makes it different from other sugars is how the body treats it.

Lustig noted that fructose can only be metabolized by the liver, unlike glucose, which can be used by all organs of the body.

In the liver, fructose is phosphorylated, which depletes phosphate levels in the liver and increases uric acid production, he added.

"The liver is under greater substrate pressure with fructose than with glucose, which means you'll gen[erate] more uric acid for the same number of calories," Lustig said.

Once in the bloodstream, uric acid inhibits endothelial nitric oxide synthase (eNOS), thus reducing the production of the nitric oxide essential for keeping the vessels flexible. In turn, that leads to high blood pressure, Lustig said.

Either way, Johnson added, the take-home message is that "we should probably reduce our intake of added sugars, and that the benefits may be greater than simple weight loss."

While the researchers "aren't ready to recommend lowering uric acid as a means to treat blood pressure," he said, the study suggests further "examining the role of uric acid in blood pressure."

Johnson reported financial relationships with Merck and a patent application related to lowering uric acid as a means of treating hypertension and metabolic syndrome.

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